Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a human glycoprotein which is also known under the name CD66a (Cluster of Differentiation 66a). It belongs to the “carcinoembryonic antigen” gene family. This family includes two subgroups, namely the subgroup of cell adhesion molecules, which include CEACAM1, and also the subgroup of the pregnancy-specific glycoproteins.
It is known that CEACAM1 is a specific cell-cell adhesion molecule which is present on leucocytes, epithelial cells and endothelial cells. Cells that express CEACAM1 on their surface, however, also release it into the blood stream. The glycoprotein mediates the cell adhesion by means of homophilic or heterophilic binding to other proteins of the cell adhesion molecule subgroup.
It is further known that diverse cell activities such as, for example, differentiation and the arrangement of three-dimensional tissue structures, angiogenesis, apoptosis, tumor suppression and metastasis, can be influenced by CEACAM1.
The publication by Singer et al. (“Adhesion Molecule 1 Expression and Carcinoembryonic Antigen-Related Cell Signaling in Human, Mouse, and Rat Leukocytes: Evidence for Replacement of the Short Cytoplasmic Domain Isoform by Glycosylphosphatidylinositol-Linked Proteins in Human Leukocytes”, Bernhard B. Singer, Inka Scheffrahn, Robert Heymann, Kristmundur Sigmundsson, Robert Kammerer and Björn Öbrink, The Journal of Immunology (2002), vol. 168, 5139-5146) is concerned with studies of expression of CEACAM1 on leucocytes of humans, mice and rats.
The publication by Greicius et al. (“CEACAM1 is a Potent Regulator of B Cell Receptor Complexinduced Activation”, Gediminas Greicius, Eva Severinson, Nicole Beauchemin, Björn Öbrink and Bernhard B. Singer, Journal of Leukocyte Biology (2003), vol. 74, 126-134) mentions that CEACAM1 regulates the tumor growth of epithelial cells, angiogenesis, NK-cell cytotoxicity and also T cell cytotoxicity.
The publication by Chen et al. (“Editorial: CEACAM1: fine-tuned for fine-tuning”, Zhangguo Chen, Lanfen Chen and Richard S. Blumberg, Journal of Leukocyte Biology (2009), vol. 86, 195-197) underlines the importance of CEACAM1 in relation to tumor genesis, angiogenesis and metabolism.
The publication by Lobo et al. (“Pivotal Advance: CEACAM1 is a Negative Coreceptor for the B Cell Receptor and Promotes CD19-mediated Adhesion of B Cells in a PI3K-dependent Manner”, Elizabeth O. Lobo, Zhifang Zhang and John E. Shively, Journal of Leukocyte Biology (2009), vol. 86, 205-218) discloses that CEACAM1 is a negative receptor for what is termed the B cell receptor (BCR).
The publication by Blau et al. (“Targeted Disruption of the Ceacam1 (MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection”, Dianna M. Blau, Claire Turbide, Michel Tremblay, Melanie Olson, Stéphanie Létourneau, Eva Michaliszyn, Serge Jothy, Kathryn V. Holmes and Nicole Beauchemin, Journal of Virology (2001), vol. 75, 8173-8186) discloses that CEACAM1-Knockout mice are less susceptible to a hepatitis infection.
WO 2005/058358 A2 discloses fusion proteins derived from CEACAM1 in the context of inflammatory diseases.
U.S. Pat. No. 8,598,322 B2 and also WO 2013/054331 A1 each disclose anti-CEACAM1 antibodies, and also use thereof for the treatment of cancer.
WO 2013/082366 A1 discloses CEACAM1-antibodies for tumor treatment, in particular cancer treatment.
WO 2013/054331 A1 addresses CEACAM1 antibodies in the context of the treatment of viral infections and cancers.
In WO 2014/022332 A1, a composition is described which modulates the interaction between TIM3 and CEACAM1.
Although the potential use of CEACAM1 as what is termed a therapeutic target has been recognized in principle, to date many questions with respect to therapeutic usability of CEACAM1 as a target have still not been clarified. In particular, to date there are contradictory data as to whether CEACAM1 is expressed on B cells and to what extent CEACAM1-binding substances, in particular antibodies, are able to influence B cells in vitro.
Likewise, to date the usability of CEACAM1 for activating other cells of the immune system, such as T cells, for instance, is unknown.
There continues to be a great need for the development of therapeutically effective substances, the therapeutic target of which is CEACAM1.